The formation of biofilms on the surface of medical devices is a serious and increasing problem for the medical community. Biofilms form on many types of surfaces, composed of a wide variety of materials, including catheters and ports, metal surfaces such as implanted prosthetic devices, live tissue such as deep wound trauma areas, and oral tissues such as teeth, gum tissue and bone. A number of types of organisms can originate biofilms including bacteria and fungi. Further, while some biofilms can be occupied by a single species, more commonly biofilms consist of an entire community of a variety of organisms. In some cases, even viruses can participate in the pathology generated by the biofilm community by way of bacteriophages. Both gram-negative and gram-positive bacterial organisms as well as fungi can produce biofilms.
While occupying a biofilm, many organisms, especially pathogens, exhibit a changed profile of sensitivities or resistances to antibiotics. This, coupled with the physico-chemical protections provided by the biofilm, make treating patients with biofilm infections very difficult. The problem is increasingly difficult as more organisms become antibiotic resistant, even when means can be found to deliver an effective dose of an antibiotic to the biofilm occupants.
An additional problem arises when trying to design an antimicrobial treatment to destroy a biofilm infection utilizing either small molecule agents or antibiotic agents that are strongly effective against planktonic forms of biofilm organisms. The problem lies in the inability of the antimicrobial agents, such as antibiotics, to penetrate the biofilm due in part to the biofilm acting to protect the embedded microorganisms by preventing or reducing the antibiotic diffusion, thus only reaching the target organisms in lowered concentration. One means by which this form of barrier could operate is to react with the incoming antimicrobial agent at or near the surface, converting it into a different and potentially less lethal form. Another mechanism is physiology-based, positing that the biofilm-bound organisms are essentially undergoing modified metabolic process, relative to the planktonic counterparts, the modification of which reduces their susceptibility to the antibiotic agent. Thus, the design of effective antimicrobial agents has presented many challenges.
During a microbial infection, various cellular stress responses are also triggered, leading to tissue inflammation and immune cell activation. These immune events, in turn, may promote the development of and/or sustain pathways that underlie downstream disorders such as cancer. However, molecular events linking these processes are not well understood, hindering efforts to uncover effective immune modulators that may be useful for the treatment of downstream immune-associated conditions.